Acoustofluidic-based therapeutic apheresis system

Therapeutic apheresis aims to selectively remove pathogenic substances, such as antibodies that trigger various symptoms and diseases. Unfortunately, current apheresis devices cannot handle small blood volumes in infants or small animals, hindering the testing of animal model advancements. This limitation restricts our ability to provide treatment options for particularly susceptible infants and children with limited therapeutic alternatives. Here, we report our solution to these challenges through an acoustofluidic-based therapeutic apheresis system designed for processing small blood volumes. Our design integrates an acoustofluidic device with a fluidic stabilizer array on a chip, separating blood components from minimal extracorporeal volumes. We carried out plasma apheresis in mouse models, each with a blood volume of just 280 μL. Additionally, we achieved successful plasmapheresis in a sensitized mouse, significantly lowering preformed donor-specific antibodies and enabling desensitization in a transplantation model. Our system offers a new solution for small-sized subjects, filling a critical gap in existing technologies and providing potential benefits for a wide range of patients.


Note S1: Simulation models
We have incorporated two sets of fluid stabilizers into the circulation system to effectively tackle challenges stemming from fluctuating blood pressure and the instability induced by peristaltic pumps.Each fluidic stabilizer consists of four cavities connected to the main fluid microchannel.Supplementary Fig. 1 illustrates the cross-section view and corresponding models of these fluids.
As shown in Supplementary Fig. 1, when in steady state, the pressure in the n th conjunction of side-channel 2 and the main channel is   , with a flow rate of  , in the main channel.Due to Poiseuille's Law, and according to the Euler equation ( 1) where  is the density of the fluid,  1, is the cross-section area of the n th main channel,  1, is the length of the n th stabilizers on the main channel, and  1, is the flow resistance of the n th main channel.During the stabilization process in the channel, we assume that the flow rate of the outlet increases by ∆ , when the pressure changes by ∆  .Thus, the force balance near the outlet of the channel can be expressed as After substituting Eq. ( 1) into the Eq. ( 2), the force balance near the outlet can be rewritten as The side channel can thus be considered as a mass-spring system.The total mass inside of the cavity can be assumed to be a constant.Considering that the volume change is much smaller than the cavity volume and that the temperature reaches steady state in less than 200 µs in ambient area ( = 1), The pressure inside of the n th side channel can be expressed as ( 2) Which can also be rewritten as Where ∆  =  2, ∆ 2, represents the volume change inside of the side channel, and  2, and  2, represent the initial pressure and volume of the trapped air in the side channel and cavity, respectively.
Which can be expressed as Since the change in volume is much smaller than cavity volume (∆  ≪  2, ), we neglect the higher order terms of the Taylor series, yielding Thus, by considering the forces of the flow column, the force balance inside the side channel connected to the cavity can be expressed as where  2, is the initial pressure,  2, is the initial volume of the trapped air,  is the density of fluid,  2, is the cross-section are, ∆ 2, is the flow column increasement, and  2, is the flow resistance of the n th side channel, respectively. 2, is the flow rate in the side channel.∆ 2, is the increase in flow rate in the side channel, which has the following connection with the inlet and outlet flow rate: Where the inlet and outlet flow rate have the following equations by considering the total flow rate in the main channel By applying the Laplace transformation to Eqs. (3) and (9), the pressure change inside of the n th main channel and side channel can be expressed as Since ∆  = ∆ 2,  2, = ∫ ∆ 2, / 2, , Eq. ( 14) can be expressed as Where ∆′ , , ∆′ 2, represent the Laplace term.
Hence, the relationship between the volume flow rate out of the n th main channel and the volume flow rate inside the n th side channel can be expressed by the following equations: and where and where As shown in Supplementary Fig. 1, the fluid stabilizers are periodically attached to the main channel.We can assume that the initial parameters for each stabilizer are the same.Thus, the increase in flow rate in the n th outlet can be expressed as Combining Eq. ( 11) and ( 12), yields By considering the flow rate continuity conditions between the n th main stabilizer and (n-1) th stabilizer, ∆ , = ∆ ,−1 , we can deduce that the relationship between the flow rate in the 1 st stabilizer and the flow rate in the last stabilizer has the following relation: The Laplace transform thus also has the following relationship Therefore, Eq. ( 23) and Eq. ( 24) can be rewritten as And By considering that the inlet flow rate  ,1 has an initial disturbance of ∆ ,1 from the steady inlet flow rate  ,1 , we yield the following equation expression.
Where  is the disturbance ratio, and  is the disturbance frequency.
As shown in Supplementary Fig. 2, the flow rate increase, ∆ ,1 , thus has the following expression.

∆𝑄
outlet flow rate change can be obtained and expressed as 6